This invention relates to a process for the de-esterification of cephalosporin esters. In particular, it relates to a process for the de-esterification of p-nitrobenzyl esters of cephalosporins. Esters of cephalosporins are commonly employed intermediates in the synthesis of cephalosporin antibiotics in the free acid form. The ester function is generally employed to block or protect the acidic carboxylic acid function in the molecule while reactions at other sites in the molecule are carried out. For example, Garbrecht, U.S. Pat. No. 3,632,850 describes the use of the p-nitrobenzyl ester group in the synthesis of cephalexin. In the final step of the synthesis, this ester is cleaved via hydrogenolysis under acidic conditions. Garbrecht later describes in U.S. Pat. No. 3,781,282 the de-esterification of p-nitrobenzyl esters of cephalosporins with zinc and acid in an amide-type solvent, for example in dimethylformamide. Jackson, U.S. Pat. No. 3,799,924 describes the removal of the p-nitrobenzyl ester group of cephalosporins on treatment of the ester with sodium or potassium dithionite at a pH above about 7. More recently, in copending application Ser. No. 701,850, filed July 1, 1976, Hatfield describes a process for de-esterifying certain penicillin and cephalosporin esters including the p-nitrobenzyl ester group which comprises a reductive cleavage employing zinc and organothiols, e.g., benzenethiol.
Because of the importance of the p-nitrobenzyl esters of cephalosporin antibiotics in the synthesis of these antibiotics in the free acid antibiotic form, improved or alternative methods for the removal of this ester group continue to be the subject of investigation.